Citalopram is an important anti-depression drug, which is a selective 5-hydroxytryptamine (5-HT) reuptake inhibitor with S-configuration, and the isomer with S-citalopram has an anti-depression effect that is 100 times more than the isomer of the opposite configuration—R-citalopram, therefore, it has a much better curative effect and much less dosage. In the market of Europe and America, the S-isomer is mainly sold, and it is prepared by the cyclization and salt-forming reaction of S-5-cyano did (IV).
S-5-cyano diol (IV) is the key initial raw material for producing S-citalopram, in industrial production, generally, it is prepared by forming a salt from racemic 5-cyano diol (I) and a resolving agent D-(+)di-p-toluoyl tartaric acid (II) (abbr. DPTTA) in alcohols and mixed solvents comprising alcohols, separating the (S)-5-cyano did resolved intermediate (III) by crystallization, then subjecting to ionization by a free base. The resolution process can be represented as follows:

The structure of the resolving agent DPTTA is as follows:

In U.S. Pat. No. 4,943,590 and WO2007/012954, it is described that the (S)-5-cyano diol resolved intermediate (III) is obtained by the resolution of racemic 4-(4-dimethylamino-1-p-fluorophenyl-1-hydroxybutyl)-3-(hydroxymethyl) benzonitrile by DPTT in isopropanol. The particle size of the crystals of the (a)-5-cyano diol resolved intermediate (III) obtained by the method are small and they are hard to be filtered, which does not meet the requirement of large-scale industrial production, and the chiral purity of the obtained crude (S)-5-cyano dial resolved intermediate (III) is low, the crude product needs to be repurified by isopropanol during the production to be qualified, thus the operation is very complex.
US2009/0069582 reports the preparation of the (S)-5-cyano diol resolved intermediate (III) with DPTT as the resolving agent, resolving racemic 5-cyano dial (I) from the solvent system comprising 1-propanol. The chiral purity of the method is generally low, two times of refinements are needed during production to obtain the (S)-5-cyano diol resolved intermediate (III) with qualified chiral purity, and the yield of the method is smaller than 38% at present.